scholarly journals A GAIN in understanding autoproteolytic G protein-coupled receptors and polycystic kidney disease proteins

2012 ◽  
Vol 31 (6) ◽  
pp. 1334-1335 ◽  
Author(s):  
John J G Tesmer
Keyword(s):  
Kidney Disease ◽  
G Protein ◽  
Polycystic Kidney Disease ◽  
G Protein Coupled Receptors ◽  
Polycystic Kidney ◽  
G Protein Coupled

scholarly journals Heterotrimeric G protein signaling in polycystic kidney disease

2016 ◽  
Vol 48 (7) ◽  
pp. 429-445 ◽  
Author(s):  
Taketsugu Hama ◽  
Frank Park
Keyword(s):  
Kidney Disease ◽  
G Protein ◽  
Polycystic Kidney Disease ◽  
G Proteins ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Polycystic Kidney ◽  
Heterotrimeric G Protein ◽  
Heterotrimeric G Protein Signaling

Autosomal dominant polycystic kidney disease (ADPKD) is a signalopathy of renal tubular epithelial cells caused by naturally occurring mutations in two distinct genes, polycystic kidney disease 1 ( PKD1) and 2 ( PKD2). Genetic variants in PKD1, which encodes the polycystin-1 (PC-1) protein, remain the predominant factor associated with the pathogenesis of nearly two-thirds of all patients diagnosed with PKD. Although the relationship between defective PC-1 with renal cystic disease initiation and progression remains to be fully elucidated, there are numerous clinical studies that have focused upon the control of effector systems involving heterotrimeric G protein regulation. A major regulator in the activation state of heterotrimeric G proteins are G protein-coupled receptors (GPCRs), which are defined by their seven transmembrane-spanning regions. PC-1 has been considered to function as an unconventional GPCR, but the mechanisms by which PC-1 controls signal processing, magnitude, or trafficking through heterotrimeric G proteins remains to be fully known. The diversity of heterotrimeric G protein signaling in PKD is further complicated by the presence of non-GPCR proteins in the membrane or cytoplasm that also modulate the functional state of heterotrimeric G proteins within the cell. Moreover, PC-1 abnormalities promote changes in hormonal systems that ultimately interact with distinct GPCRs in the kidney to potentially amplify or antagonize signaling output from PC-1. This review will focus upon the canonical and noncanonical signaling pathways that have been described in PKD with specific emphasis on which heterotrimeric G proteins are involved in the pathological reorganization of the tubular epithelial cell architecture to exacerbate renal cystogenic pathways.

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